Chen Da-Yuan, Khan Nazimuddin, Close Brianna J, Goel Raghuveera K, Blum Benjamin, Tavares Alexander H, Kenney Devin, Conway Hasahn L, Ewoldt Jourdan K, Kapell Sebastian, Chitalia Vipul C, Crossland Nicholas A, Chen Christopher S, Kotton Darrell N, Baker Susan C, Connor John H, Douam Florian, Emili Andrew, Saeed Mohsan
bioRxiv. 2020 Oct 28:2020.10.27.358259. doi: 10.1101/2020.10.27.358259.
SARS-CoV-2 can infect multiple organs, including lung, intestine, kidney, heart, liver, and brain. The molecular details of how the virus navigates through diverse cellular environments and establishes replication are poorly defined. Here, we performed global proteomic analysis of the virus-host interface in a newly established panel of phenotypically diverse, SARS-CoV-2-infectable human cell lines representing different body organs. This revealed universal inhibition of interferon signaling across cell types following SARS-CoV-2 infection. We performed systematic analyses of the JAK-STAT pathway in a broad range of cellular systems, including immortalized cell lines and primary-like cardiomyocytes, and found that several pathway components were targeted by SARS-CoV-2 leading to cellular desensitization to interferon. These findings indicate that the suppression of interferon signaling is a mechanism widely used by SARS-CoV-2 in diverse tissues to evade antiviral innate immunity, and that targeting the viral mediators of immune evasion may help block virus replication in patients with COVID-19.
严重急性呼吸综合征冠状病毒2（SARS-CoV-2）可感染多个器官，包括肺、肠道、肾脏、心脏、肝脏和大脑。关于该病毒如何在不同细胞环境中穿梭并建立复制的分子细节尚不清楚。在此，我们在一组新建立的、代表不同身体器官的、表型多样且可被SARS-CoV-2感染的人类细胞系中，对病毒-宿主界面进行了全蛋白质组分析。这揭示了SARS-CoV-2感染后，不同细胞类型中干扰素信号传导受到普遍抑制。我们在广泛的细胞系统中，包括永生化细胞系和原代样心肌细胞，对JAK-STAT途径进行了系统分析，发现该途径的几个组分被SARS-CoV-2靶向，导致细胞对干扰素脱敏。这些发现表明，干扰素信号传导的抑制是SARS-CoV-2在不同组织中广泛用于逃避抗病毒固有免疫的一种机制，并且靶向免疫逃避的病毒介质可能有助于阻断COVID-19患者体内的病毒复制。
